Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Postinduction Treatment for Specific ALL Subgroups
Table 3. Outcome According to Treatment Protocol for Adolescents and Young Adults with ALL continued...
Factors significantly associated with favorable prognosis in the pre-imatinib mesylate era included the following:
- Younger age at diagnosis.
- Lower leukocyte count at diagnosis.
- Early response measures.[49,50,51]
- Ph+ ALL with a rapid morphologic response or rapid peripheral blood response to induction therapy.[49,50]
Following MRD by reverse transcription polymerase chain reaction for the BCR-ABL fusion transcript may also be useful to help predict outcome for Ph+ patients.[52,53,54]
Tyrosine kinase inhibitor therapy
Imatinib mesylate is a selective inhibitor of the BCR-ABL protein kinase. Phase I and II studies of single-agent imatinib in children and adults with relapsed or refractory Ph+ ALL have demonstrated relatively high response rates, although these responses tended to be of short duration.[55,56]
Clinical trials in adults and children with Ph+ ALL have demonstrated the feasibility of administering imatinib mesylate in combination with multiagent chemotherapy.[57,58,59] Preliminary outcome of results for Ph+ ALL demonstrated a better outcome after HSCT if imatinib was given before or after transplant.[60,61,62,63]
Evidence (imatinib mesylate):
- The COG-AALL0031 study evaluated whether imatinib mesylate could be incorporated into an intensive chemotherapy regimen for children with Ph+ ALL. Patients received imatinib mesylate in conjunction with chemotherapy during postinduction therapy. Some children proceeded to allogeneic SCT after two cycles of consolidation chemotherapy with imatinib mesylate, while other patients received imatinib mesylate in combination with chemotherapy throughout all treatment phases.
- The 3-year EFS for the 25 patients who received intensive chemotherapy with continuous dosing of imatinib mesylate is 87.7% ± 10.9%. These patients fared better than historic controls treated with chemotherapy alone (without imatinib mesylate), and at least as well as the other patients on the trial who underwent allogeneic transplantation. Longer follow-up is necessary to determine whether this novel treatment improves cure rate or merely prolongs DFS.
Dasatinib, a second-generation inhibitor of tyrosine kinases, is currently being studied in the initial treatment of Ph+ ALL. Dasatinib has shown significant activity in the CNS, both in a mouse model and a series of patients with CNS-positive leukemia.
Treatment options under clinical evaluation for Philadelphia chromosome–positive ALL
Treatment options under clinical evaluation include the following:
- COG-AALL1122 (NCT01460160) (Pediatric Ph+ ALL): In this international collaborative study, patients receive dasatinib, which has increased affinity for BCR/ABL1, in conjunction with a chemotherapy backbone based on the European EsPhALL regimen. Allogeneic SCT in first remission is reserved for those patients with suboptimal early response to therapy, as measured by morphology and MRD techniques. The goals of this study include the following:
- To determine the safety and feasibility of administering dasatinib with this chemotherapy regimen.
- To determine the 3-year EFS of patients treated in this manner.
- To compare outcomes with patients treated on prior trials using similar chemotherapy with imatinib mesylate.